7ZJM

Crystal structure of a complex between CspZ from Borrelia burgdorferi strain B408 and human FH SCR domains 6-7

Summary for 7ZJM

• Entry DOI: 10.2210/pdb7zjm/pdb
• Descriptor: CspZ, Complement factor H, ZINC ION, ... (6 entities in total)
• Functional Keywords: lyme disease, complement system, borreliosis, bbh06., immune system
• Biological source: Borreliella burgdorferi (Lyme disease spirochete); More
• Total number of polymer chains: 2
• Total formula weight: 40739.59

Authors

Brangulis, K.,Marcinkiewicz, A.,Hart, T.M.,Dupuis, A.P.,Zamba Campero, M.,Nowak, T.A.,Stout, J.L.,Akopjana, I.,Kazaks, A.,Bogans, J.,Ciota, A.T.,Kraiczy, P.,Kolokotronis, S.O.,Lin, Y.-P. (deposition date: 2022-04-11, release date: 2023-04-19, Last modification date: 2024-10-23)

Primary citation

Marcinkiewicz, A.L.,Brangulis, K.,Dupuis 2nd, A.P.,Hart, T.M.,Zamba-Campero, M.,Nowak, T.A.,Stout, J.L.,Akopjana, I.,Kazaks, A.,Bogans, J.,Ciota, A.T.,Kraiczy, P.,Kolokotronis, S.O.,Lin, Y.P.
Structural evolution of an immune evasion determinant shapes pathogen host tropism.
Proc.Natl.Acad.Sci.USA, 120:e2301549120-e2301549120, 2023

PubMed Abstract: Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease-causing bacterium () is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick-transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement-mediated immune clearance, produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH-binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host-specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, and identifying minor variation localized in the FH-binding interface yielding bird and rodent FH-specific binding activity that impacts infectivity. Swapping the divergent region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. We further linked these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism.

PubMed: 37364114
DOI: 10.1073/pnas.2301549120

Experimental method

X-RAY DIFFRACTION (2.59 Å)